Lactoperoxidase (LP), hydrogen peroxide (H2O2) and thiocyanate ion (SCN-) form a bacteriostatic system in human saliva. The oral "lactic-acid bacteria" release H2O2 as a by-product of carbohydrate metabolism. Stimulated leukocytes in the salivary glands, oral mucosa, and saliva may also produce H2O2 and secrete peroxidase enzymes. Peroxidases catalyze the oxidation of SCN- by H2O2 to yield hypothiocyanine ion (OSCN-), which is in acid-base equilibrium with hypothiocyanous acid (HOSCN). HOSCN oxydizes essential sulfhydryl groups of bacterial enzymes and transport systems, resulting in inhibition of metabolism and growth. Certain bacteria such as S. mutans have a limited resistance to inhibition, due to their ability to rapidly reduce certain disulfide compounds to the sulfhydryl forms. These sulfhydryl compounds protect essential protein sulfhydryls by reacting with the inhibitor and reducing it back to SCN-. These studies will establish a method for measuring LP antibacterial activity in saliva against the bacteria present in the saliva sample. Using this method, the effects of agents that may increase LP antibacterial will be examined. These agents increase the supply of peroxides, change the LP system so as to produce a more potent inhibitor, or inhibit bacterial enzymes involved in resistance. Additional studies will determine mechanisms and examine specificity of activity against S. mutans, other oral streptococci, and bacterial that usually do not colonize the mouth. The contribution of leukocytes to SCN--dependent antimicrobial activity will be studied by stimulating leukocyte H2O2 production in saliva and measuring leukocyte peroxidase enzymes. These studies will provide information about the interaction of the peroxidase system with the bacteria that can survive and grow in the presence of this antimicrobial system. The studies should also provide a basis for evaluating the significance of the LP system in natural resistance to oral disease, (1) by developing methods to measure Lp antimicrobial activity that could be used in the clinical environment, and (2) by identifying agents that can increase the efficacy or selectivity of antimicrobial action against oral pathogens. Such agents could then be used to compare the effect of the LP system in the normal population with the effect in a population receiving the agent.